Matches in SemOpenAlex for { <https://semopenalex.org/work/W1917900907> ?p ?o ?g. }
- W1917900907 endingPage "1024" @default.
- W1917900907 startingPage "1006" @default.
- W1917900907 abstract "The forkhead box (FOX), FOXO1 and FOXO3, transcription factors regulate multiple functions in mammalian cells. Selective inactivation of the Foxo1 and Foxo3 genes in murine ovarian granulosa cells severely impairs follicular development and apoptosis causing infertility, and as shown here, granulosa cell tumor (GCT) formation. Coordinate depletion of the tumor suppressor Pten gene in the Foxo1/3 strain enhanced the penetrance and onset of GCT formation. Immunostaining and Western blot analyses confirmed FOXO1 and phosphatase and tensin homolog (PTEN) depletion, maintenance of globin transcription factor (GATA) 4 and nuclear localization of FOXL2 and phosphorylated small mothers against decapentaplegic (SMAD) 2/3 in the tumor cells, recapitulating results we observed in human adult GCTs. Microarray and quantitative PCR analyses of mouse GCTs further confirmed expression of specific genes (Foxl2, Gata4, and Wnt4) controlling granulosa cell fate specification and proliferation, whereas others (Emx2, Nr0b1, Rspo1, and Wt1) were suppressed. Key genes (Amh, Bmp2, and Fshr) controlling follicle growth, apoptosis, and differentiation were also suppressed. Inhbb and Grem1 were selectively elevated, whereas reduction of Inha provided additional evidence that activin signaling and small mothers against decapentaplegic (SMAD) 2/3 phosphorylation impact GCT formation. Unexpectedly, markers of Sertoli/epithelial cells (SRY [sex determining region Y]-box 9/keratin 8) and alternatively activated macrophages (chitinase 3-like 3) were elevated in discrete subpopulations within the mouse GCTs, indicating that Foxo1/3/Pten depletion not only leads to GCTs but also to altered granulosa cell fate decisions and immune responses. Thus, analyses of the Foxo1/3/Pten mouse GCTs and human adult GCTs provide strong evidence that impaired functions of the FOXO1/3/PTEN pathways lead to dramatic changes in the molecular program within granulosa cells, chronic activin signaling in the presence of FOXL2 and GATA4, and tumor formation." @default.
- W1917900907 created "2016-06-24" @default.
- W1917900907 creator A5014896169 @default.
- W1917900907 creator A5028958519 @default.
- W1917900907 creator A5029456681 @default.
- W1917900907 creator A5039851941 @default.
- W1917900907 creator A5044931412 @default.
- W1917900907 creator A5083576721 @default.
- W1917900907 creator A5089399049 @default.
- W1917900907 creator A5090922860 @default.
- W1917900907 date "2015-07-01" @default.
- W1917900907 modified "2023-10-12" @default.
- W1917900907 title "FOXO1/3 and PTEN Depletion in Granulosa Cells Promotes Ovarian Granulosa Cell Tumor Development" @default.
- W1917900907 cites W1498970130 @default.
- W1917900907 cites W1499500424 @default.
- W1917900907 cites W1531523780 @default.
- W1917900907 cites W1555534494 @default.
- W1917900907 cites W1908134412 @default.
- W1917900907 cites W1966990623 @default.
- W1917900907 cites W1971546287 @default.
- W1917900907 cites W1976722903 @default.
- W1917900907 cites W1977679887 @default.
- W1917900907 cites W1978659152 @default.
- W1917900907 cites W1979014323 @default.
- W1917900907 cites W1979045512 @default.
- W1917900907 cites W1979134116 @default.
- W1917900907 cites W1981935668 @default.
- W1917900907 cites W1984220883 @default.
- W1917900907 cites W1987441485 @default.
- W1917900907 cites W1990440494 @default.
- W1917900907 cites W1994699166 @default.
- W1917900907 cites W1995012620 @default.
- W1917900907 cites W1995380492 @default.
- W1917900907 cites W1996199571 @default.
- W1917900907 cites W1997148372 @default.
- W1917900907 cites W1997294930 @default.
- W1917900907 cites W1999074070 @default.
- W1917900907 cites W2001215570 @default.
- W1917900907 cites W2002638967 @default.
- W1917900907 cites W2004012343 @default.
- W1917900907 cites W2005071828 @default.
- W1917900907 cites W2010637356 @default.
- W1917900907 cites W2013377366 @default.
- W1917900907 cites W2013881488 @default.
- W1917900907 cites W2015533701 @default.
- W1917900907 cites W2015971275 @default.
- W1917900907 cites W2016746345 @default.
- W1917900907 cites W2017008764 @default.
- W1917900907 cites W2019822707 @default.
- W1917900907 cites W2019954526 @default.
- W1917900907 cites W2021528515 @default.
- W1917900907 cites W2023375567 @default.
- W1917900907 cites W2026250050 @default.
- W1917900907 cites W2026674119 @default.
- W1917900907 cites W2029872286 @default.
- W1917900907 cites W2031287458 @default.
- W1917900907 cites W2031850977 @default.
- W1917900907 cites W2035066075 @default.
- W1917900907 cites W203562767 @default.
- W1917900907 cites W2036509369 @default.
- W1917900907 cites W2036819335 @default.
- W1917900907 cites W2037341437 @default.
- W1917900907 cites W2038988941 @default.
- W1917900907 cites W2039965654 @default.
- W1917900907 cites W2041828252 @default.
- W1917900907 cites W2042410624 @default.
- W1917900907 cites W2042633087 @default.
- W1917900907 cites W2044491985 @default.
- W1917900907 cites W2044574558 @default.
- W1917900907 cites W2045907249 @default.
- W1917900907 cites W2051213236 @default.
- W1917900907 cites W2056616628 @default.
- W1917900907 cites W2062006818 @default.
- W1917900907 cites W2062626814 @default.
- W1917900907 cites W2064875738 @default.
- W1917900907 cites W2066801022 @default.
- W1917900907 cites W2068364416 @default.
- W1917900907 cites W2074655523 @default.
- W1917900907 cites W2076103389 @default.
- W1917900907 cites W2078292875 @default.
- W1917900907 cites W2078875366 @default.
- W1917900907 cites W2079911879 @default.
- W1917900907 cites W2082340082 @default.
- W1917900907 cites W2083574570 @default.
- W1917900907 cites W2090716605 @default.
- W1917900907 cites W2090968329 @default.
- W1917900907 cites W2093752260 @default.
- W1917900907 cites W2097989235 @default.
- W1917900907 cites W2098522854 @default.
- W1917900907 cites W2100063887 @default.
- W1917900907 cites W2101651255 @default.
- W1917900907 cites W2102112763 @default.
- W1917900907 cites W2110969580 @default.
- W1917900907 cites W2112488010 @default.
- W1917900907 cites W2118506472 @default.
- W1917900907 cites W2118912793 @default.
- W1917900907 cites W2123624440 @default.
- W1917900907 cites W2124261225 @default.